Hyperostosis induced by the bisphosphonate (2-PEBP) in the oophorectomized rat

To prevent the high turnover bone remodeling associated with acute estrogen deficiency, the bisphosphonate [2-(2-pyridinyl) ethylidene-BP] (2-PEBP) was administered to oophorectomized (OX) rats. Three groups of 15 rats each (250 g) were studied. Group (Gp) A was sham operated, Gp B was OX, and Gp C received 2-PEBP (1.72 mg/kg/day) intraperitoneally for 3 days commencing 4 days postoophorectomy. Oophorectomy was confirmed with serum estradiol measurements. Blood samples were collected on days -7, 0, 7, 14, 21, and 28 for ionized calcium (Ca2+), PTH, and serum bone gla protein (BGP). Rats received tetracycline for bone histomorphometric labeling. All results were compared to Gp A. Body weight increased significantly in Gps B and C (P less than 0.005 by day 28). There was no significant difference in Ca2+, and PTH levels in Gps B and C were similar to Gp A. BGP levels were significantly higher on day 28 in Gp B (P less than 0.05). In Gp C, BGP levels were significantly decreased on days 7, 21, and 28 (P less than 0.03). Gp B revealed increased bone turnover without loss of bone volume (BV/TV). BV/TV was significantly increased in Gp C despite a decrease in parameters of bone formation and normal osteoclast number. In conclusion, 2-PEBP in the OX rat inhibited bone resorption more than formation with resultant hyperostosis. Serum BGP appeared to be a good marker of the changes observed on bone histomorphometry.